Dirk De Ruysscher, MD, PhD: The dosage fractionation of radiation is calculated in a way that we try to avoid the normal tissues as much as possible. What we did in the past was a lot of experimental work to individualize the dose of radiation, and that is a quite good way to have the same toxicity and to increase the dose as much as possible. This works only in the normal concurrent schedule. From the moment that you give chemotherapy with radiation, there is no argument, and we have published this recently: there’s no argument to increase the dose above 60 gray in 30 fractions in an individualized way.

The only thing you then do is to make it either more complex or to make it more toxic. So in the framework of immune treatment, we have the results of the PACIFIC study, and it is shown that the addition of durvalumab after chemoradiation really increases survival in the long run, so there’s no question about that. At this moment, according to the standard of care and taking into account the RTOG 0617 study from the United States, probably it’s better to give them 60 gray in 30 daily fractions as a standard of care schedule. When it comes to sequential chemoradiation, then there’s level 1 evidence that is better and you could use 2.75 gray per fractions up to 66 gray. And that’s a way to give radiation, and it’s always according to individualized schedules for the tissues at risk, so like the lungs and the heart.

Three adverse effects that are the most important ones to be discussed are infection, esophagitis, and pneumonitis. There are some other adverse effects that should be discussed as well, but that depends more individually on the place of the tumor, what you expect from adverse effects in certain situations, depending also on some comorbidities, other diseases of patients. But in general, infections, which relate to neutropenia due to chemotherapy. At the same time as the occurrence of neutropenia, patients may have esophagitis. And because of the esophagitis, this is a way for the entrance of bacteria and viruses in the bloodstream. And hence, they can provoke septicemia, so that’s important.

Second is esophagitis, which occurs after about 3 weeks and heals after 6 to 8 weeks. We discuss with the patient supportive care measures like medication, not only painkillers but also PPIs [proton pump inhibitors] to suppress gastric acidity. And also the need for foods, so that’s nutrition advice from a dietician from the onset before the problems start because otherwise there will be a decrease of the general condition of the patient and an increase of infection susceptibility. And third is pneumonitis, which in most cases, is something that happens 2 months to 6 months after the end of treatment and can be handled by 3 weeks of corticosteroids. But I should stress that the most important thing to discuss with patients is quitting smoking, good foods, and physical exercise.

Specifically for radiation during treatment, the most important [adverse] effect is esophagitis. What we give them, first of all, prophylactically we give PPIs because we know when the esophagus is irradiated, you have more reflux, so it’s better to treat it like reflux esophagitis. And that means that the PPI should be given at least 2 or 3 months post-treatment as well. Second, nutrition is probably the most important one, not only to keep the weight of the patient constant but even more important, to increase the quality of the food because we know there’s muscle wasting. There’s a lot of protein need, probably between 1 and 1.5 gram of protein per kg per day, so that’s massive. The nutritional support is very important because otherwise patients will have muscle wasting and cachexia even, and that is to be avoided obviously.

That also fits into the supportive care, taking into account physical exercise, some fitness and very importantly, quitting smoking. Because if you quit smoking, you decrease the probability for important adverse effects by 50%. And you decrease also approximately by 50% the duration of the adverse effects. So you have every argument to quit smoking, but that’s not easy for patients who smoked, in most cases, already 30 or 40

Transcript Edited for Clarity